Study Selection Original accounts or investigations of bed bugs, clinical responses with sufficient detail of cause and effect between the bed bug bite and clinical response, and convincing evidence of substantiated presence of bed bug exposure. For pest control, documentation that an eradication measure quantitatively decreased bed bugs.

Data Extraction A trained medical reference librarian assisted with the literature search. Two authors with expertise in the diagnosis, treatment, and eradication of bed bugs reviewed the clinical articles. One author evaluated the pest control articles.

Data Synthesis Fifty-three articles met inclusion criteria and were summarized. Only 2 clinical trials concerning bed bugs were identified and tested the ability of pest control interventions to eradicate bed bugs. Although transmission of more than 40 human diseases has been attributed to bed bugs, there is little evidence that they are vectors of communicable disease. A variety of clinical reactions to bed bugs have been reported, including cutaneous and rarely systemic reactions. A wide range of empirical treatments, including antibiotics, antihistamines, topical and oral corticosteroids, and epinephrine, have been used for bite reactions with varying results. No evidence-based interventions to eradicate bed bugs or prevent bites were identified.

Conclusions Treatment options for cutaneous and systemic reactions from bed bug bites have not been evaluated in clinical trials and there is no evidence that outcomes differ significantly from those receiving no treatment. Evidence for disease transmission by bed bugs is lacking. Pest control and eradication is challenging due to insecticide resistance, lack of effective products, and health concerns about spraying mattresses with pesticides.

Figures in this Article

Cimex lectularius has been known as a human parasite for thousands of years, but scientific studies of this insect are recent and limited.1,2 International travel, immigration, changes in pest control practices, and insecticide resistance may have contributed to a recent resurgence of this blood-sucking insect in developed countries.1,3 Bed bug infestations have been reported increasingly in homes, apartments, hotel rooms, hospitals, and dormitories in the United States since 1980 (Table 1).1,21,22 For example, reports of bed bug infestations in San Francisco doubled between 2004 and 2006.23 The resurgence affects other countries as well. Public health experts in Toronto, Ontario, Canada, reported a 100% increase in telephone complaints about bed bugs during a 6-month period in 2002.4 In Germany, bed bug infestations increased from 5 reported cases in 1992 to 76 cases in 2004.24 In Australia, bed bug samples submitted to a government public agency increased by 400% during the period of 2001-2004 compared with 1997-2000.25

The insect family Cimicidae contains species commonly called bed bugs, bat bugs, and swallow bugs. Bed bugs are found in temperate and tropical regions worldwide.26,27 The 91 species in this family are wingless, obligate hematophagous ectoparasites that feed on bats, birds, and mammals.26,27 The word Cimex is derived from the Roman designation for bug and lectularius from the Latin name for couch or bed. Only 2 species, Cimex lectularius and Cimex hemipterus, readily feed on humans but others may rarely do so as well.

Adult bed bugs are oval shaped, flat, and approximately 5 mm long (Figure 1A). Quiz Ref IDThey resemble unfed ticks or small cockroaches and are easily visible, even to the untrained eye. Adults are reddish brown (chestnut) in color, whereas immatures are much smaller and may be light yellow. They have a pyramid-shaped head with prominent compound eyes, slender antennae, and a long proboscis tucked underneath the head and thorax. After a blood meal, the bugs may increase in length by 30% to 50% and in weight by 150% to 200% (Figure 1B).27

Figure 1. Adult Bed Bug Before and After a Human Blood Meal Feeding

An adult bed bug before (A) and after (B) a human blood meal feeding. The bed bug is shown on a scale of 1 mm per interval.

Bed bugs sense and seek warmth, a trait that helps them locate warm-blooded hosts.27 They generally avoid light, hide during the day, and feed at night. Hiding places are usually within 1 to 2 meters of suitable hosts and include seams in mattresses, crevices in box springs, backsides of headboards, spaces under baseboards or loose wallpaper, and even behind hanging pictures. Adult bed bugs have an average life span of 6 to 12 months and can survive up to a year without feeding.

Dispersal of human-associated bed bugs generally depends on their human hosts for movement from one location to another.28 This may occur by way of furniture, clothing, suitcases, used mattresses, and other personal possessions. Bugs may also migrate from one apartment or hotel room to another through holes in walls, water pipes, or gutters.29,30

We present current knowledge of the health and medical effects of bed bugs, explore key issues in eradication efforts, and identify areas where further research is needed. Furthermore, we summarize evidence regarding whether bed bugs can serve as vectors of human disease and delineate clinical manifestations associated with bed bug bites in humans. Existing data regarding treatment of bed bug bites, prevention of bed bug bites, and bed bug eradication are also described.

METHODS

We focused our computer-assisted literature search on (1) the medical and health effects of bed bugs, and (2) pest control and eradication aspects of the bed bugs. We searched MEDLINE and EMBASE (European) databases for the period between 1960 and October 2008. Our search strategy was limited to English language papers and used the Medical Subject Heading (MeSH) term bedbugs. Additional keywords included Cimex lectularius, humans, parasitology, pathogenicity, bite reactions, hypersensitivity, skin, cutaneous, and drug effects. We also searched for publication types, including clinical trial or randomized controlled trial. For bed bug pest control and eradication information, we accessed PubMed and Toxline databases using the keywords bed bugs, Cimex, pest control, prevention, and eradication between 1960 through October 2008.

We sought information using manual searches to identify pertinent articles in sources frequently not included in computer databases. These included older journals, textbooks, pest control trade journals, and newspapers from 1892 to October 2008 in the entomology reference collection of the Mississippi E ntomological Museum at Mississippi State University, Mississippi State. We also reviewed reference lists from retrieved articles and textbooks to identify additional articles of interest. During this manual search of reference lists, we found (and included) 6 key medical articles written in German and Portuguese.

The criteria used to select studies of the health and medical effects of bed bug bites were (1) accounts or investigations that were original, (2) clinical responses with sufficient detail to allow for a reasonable conclusion of cause and effect between the bed bug bite and clinical response, and (3) convincing evidence that the reactions described were unlikely to have resulted from other insects. Specifically, we looked for information that substantiated the presence of bed bug exposure by identifying insects or their cast skins in the environment where the patient noted a clinical reaction. We also required that the description of the clinical reaction had to be sufficiently detailed (ie, dermal vs systemic, characteristics of the dermatological response, or symptoms from the systemic response) to establish that an untoward event actually occurred. Studies failing to document the presence of bed bugs, cast skins, or bed bug excreta in the environment where the reaction occurred and studies failing to identify the clinical characteristics of the reaction were excluded.

Criteria used to select studies about bed bug prevention, control, and eradication were (1) documentation of bed bugs in the environment, and (2) documentation that a prevention or eradication measure quantitatively decreased or prevented bed bugs in a specific environment. Studies primarily concerned with controlling other insects in the home environment, but which peripherally mentioned bed bugs, were excluded. Papers that reported only laboratory assays of pesticides were excluded.

A trained medical reference librarian assisted us with the literature search. Two medical entomologists (J.G. and R.D.) with expertise in the diagnosis, treatment, and eradication of bed bugs reviewed the clinical articles selected. For pest control and eradication information, 1 author (J.G.) evaluated the articles.

RESULTS

Evidence Synthesis

Seventy-five citations were identified regarding the health and medical effects of bed bugs and 39 articles met inclusion criteria and were included in the review (Figure 2). Sixty-three articles on pest control and eradication of bed bugs were identified and 14 of them met inclusion criteria and were included in the review. Only 2 clinical trials concerning bed bugs were identified, but they involved pest control interventions and not the health and medical effects. Almost all articles concerning the health and medical effects from bed bugs were case reports of 1 person or a few persons bitten, descriptions of the bite reactions, and treatments given.

Human immunodeficiency virus can be detected in bed bugs up to 8 days after ingestion of highly concentrated virus in experimental blood meals. However, no viral replication has been observed within the insects and no virus has been detected in bed bug feces.32,33 Mechanical transmission of human immunodeficiency virus has not been demonstrated using an artificial system of feeding bed bugs through membranes.33

The best candidate for human disease transmission by bed bugs is HBV. Bed bugs collected from huts in an HBV endemic area in northern Transvaal, South Africa, were hepatitis B surface antigen positive,43 as were samples collected from Senegal,42 Egypt,45 the Ivory Coast,54 and China.44 Hepatitis B surface antigen has also been shown to persist in bed bugs for more than 7 weeks after experimental feeding, but no replication of HBV was detected in the insects.34,36 Polymerase chain reaction assays have detected HBV DNA in bed bugs and their excrement up to 6 weeks after feeding on infected blood.38,39 Despite these findings, a 2-year bed bug eradication project in Gambia had no effect on rates of HBV infection, despite 100% reduction of bed bug numbers.55

To our knowledge, no study to date has demonstrated bed bug “vector competence” (the ability to acquire, maintain, and transmit an infectious agent), and an attempt to demonstrate vector competence for HBV failed in an experiment with chimpanzees.40 In that experiment, bed bugs were fed HBV-infected blood through an apparatus containing artificial skin-like membranes. Two weeks later, approximately 50% of the insects contained virus. These insects then took blood meals from chimpanzees, but no infections or seroconversions resulted in the primates. When the same blood used to infect the insects was injected into the chimpanzees, they rapidly developed HBV infection.40

Although evidence for disease transmission by bed bugs is equivocal, issues of vector competence, reactions to insect bites, embarrassment, and mental anguish have been the basis for lawsuits against landlords and lodging corporations.48

Reactions to Bed Bug Bites in Humans

Cutaneous Reactions. Our review of case reports revealed that the usual response to a bed bug bite appears to be no reaction with a barely visible punctum at the location of the bite (Table 1). Quiz Ref IDThe most common reactions for which medical attention is sought are 2- to 5-mm pruritic maculopapular, erythematous lesions at bed bug feeding sites, one per insect (Figure 3). These usually itch and, if not abraded, resolve within a week.8,9,56 The size and pruritus associated with these common reactions may increase in some individuals who experience repeated bites.6,14,57 There are no data to establish how frequently common reactions occur.

Some patients experience complex cutaneous reactions. Reports of these include pruritic wheals (local urticaria) around a central punctum, papular urticaria, and diffuse urticaria at bite sites usually noted on arising.5,16,58- 60 Bullous rashes may occur subsequent to biting events days later.61- 65 In some cases, these reactions evolve into pruritic papules or nodules that may become superinfected (impetiginous) after scratching and persist for weeks.9,14,58,66- 68 Secondary infection also may result in folliculitis, cellulitis, or an eczematoid dermatitis.67,69

Quiz Ref IDThe timing of cutaneous reactions to bed bugs may change with multiple exposures. This appears to reflect host immunological responses to salivary proteins.8,61,70- 74 Usinger27 fed a colony of bed bugs on himself weekly for 7 years and noted that his reactions progressed from delayed to immediate, with no evidence of desensitization. Three salivary proteins have been identified that may play a role in host immunological responses (a nitric oxide–liberating heme protein [nitrophorin],75 a 17-kDa anticoagulant [Factor X],76 and a 40-kDa apyrase-like nucleotide-binding enzyme77). One article12 provides evidence for an immunological response to salivary proteins as the basis for some cutaneous reactions to bed bug bites. A hotel guest noticed isolated macules after her first visit to a hotel. After a second stay at the same hotel 1 year later, macules again appeared but this time evolved over 3 days into crops of erythematous nodules with blisters.12 She was skin tested with a C lectularius salivary gland extract a year after the second hotel stay. Dermal injection of increasing concentrations of the extract resulted in a dose-related increase in the size of wheal and flare reactions that occurred within 20 minutes of injection. These wheal and flare reactions developed into papular reactions over 24 hours. The most concentrated salivary solution caused a papule with a blister. In vitro studies demonstrated that the patient had IgE specific to the nitrophorin but not the apyrase protein component of unfractionated salivary extract. This article suggests that some responses to bed bug bites are the same IgE-mediated biphasic (late-phase) reactions we have previously described to insect stings.78

Systemic Reactions. There are a few studies of systemic reactions from bed bug bites, including asthma, generalized urticaria, and anaphylaxis.63,79- 81 One study82 suggested that generalized urticaria from bed bug bites is not unusual. However, the descriptions of the “urticaria” in 1 study suggests erythema multiforme.83 In another study, a man staying in a hotel awakened during the night with severe itching and urticaria on his arm and neck; bed bugs were found in the room.84 He developed angioedema and hypotension, was hospitalized, and his electrocardiogram showed transient anterolateral ischemia. Eight months later, after an experimental bed bug bite, he developed a wheal at the bite site with generalized itching that required epinephrine administration to resolve his symptoms. A home evaluation of another man who had asthma revealed bed bugs in his bedding and an intradermal allergy skin test with an extract of bed bugs was positive.81 When his bedding was changed, the asthma symptoms ceased.

Treatment of Bed Bug Bite Reactions

Treatments of common and complex cutaneous reactions are usually symptomatic and not evidence based (Table 3). If lesions are pruritic, topical application of over-the-counter or prescription antipruritic agents (paroxime, doxepin) or intermediate potency corticosteroids (triamcinolone) may be helpful. Sites that are superinfected may benefit from topical mupirocin or systemic antibiotics. Systemic reactions to bed bug bites are treated as insect-induced anaphylaxis,70,84,85 with treatment including intramuscular epinephrine, antihistamines, and corticosteroids.

Issues in Prevention, Pest Control, and Eradication

Steps necessary for bed bug eradication include (1) proper identification of the bed bug species present, because some bat-infesting species may be found inside homes; (2) education of persons involved; (3) thorough inspection of infested and adjacent areas; (4) implementation of chemical and nonchemical control measures; and (5) follow-up to evaluate the success of eradication.86,87 Prevention of bed bug bites is best achieved with avoidance, because no repellents for the insects have been demonstrated conclusively to be effective. The mosquito repellant, oil of lemon eucalyptus, may help.88 Bed bugs and their fecal matter are easily visible (Figure 4). When sleeping in hotels or other unfamiliar environments, a prudent approach for preventing bites is to check the premises for bed bugs or their excreta. Important sites to inspect include mattress cords, cracks and crevices in box springs, and the back of headboards. Items purchased at garage sales and resale shops, especially mattresses, box springs, and bedding, should be carefully inspected for bed bugs before they are brought into homes because they may initiate an infestation.

Place holder to copy figure label and caption

Figure 4. Bed Bug and Bed Bug Excreta on a Mattress

Bed bugs are extremely difficult to eradicate1,86,89 and pest control issues relating to bed bugs and eradication procedures have been recently reviewed in detail.1,86,90 Pesticides are typically evaluated in the laboratory and less commonly in the field with demonstration-type studies, a common practice in University Extension Services. Currently, a variety of pesticides are undergoing evaluation for control of bed bugs. In general, the products have not performed as well as against other pests and eradication often requires nonchemical tactics as well. In 1 trial,55 insecticide spraying of children's dwellings effectively reduced exposure to bed bugs and, in another trial,91 insecticide-treated bed nets for malaria control helped eliminate bed bugs from infested homes. There is evidence that pyrethroid-impregnated bed nets used in many tropical countries for malaria control may be moderately effective against bed bugs.92- 94 However, these bed nets may be contributing to insecticide resistance in bed bugs.92,93

Quiz Ref IDPesticide control of bed bugs is complicated by insecticide resistance, lack of effective products, and health concerns about spraying mattresses with pesticides.1,3,88 Nonchemical methods for bed bug control include vacuuming, heat or steam treatments, mattress and box spring encasements, and discarding furnishings such as mattresses and box springs. Discarding mattresses and box springs is sometimes recommended by pest control personnel or public health authorities, but is financially burdensome.86- 88 Others recommend that mattresses and box springs be covered with encasements (similar to those used for dust mite allergies) that will not allow any remaining bugs to feed through the material or escape its confines.

COMMENT

No randomized controlled trials on bite reactions, risk factors for outbreaks, or treatment modalities were identified during this review. Two identified clinical trials involved pest control interventions. Most articles concerning health and medical effects of bed bugs consisted of case reports of 1 to 2 persons bitten and their treatment. No study designs were described in the treatment approaches.

Detailed accounts of bed bug biting incidents4- 6 demonstrate that not everyone bitten by bed bugs develops a clinical reaction, a finding supported by experimental work with volunteers that reported that only approximately 30% of patients react to bites.8 A variety of clinical reactions to bed bugs have been reported but these have not been placed into a clinically useful classification. Our review of the medical literature on this topic along with our clinical experience suggests that a useful classification of reactions should be based on local cutaneous vs systemic symptoms. Local cutaneous reactions have been reported to be uniphasic or multiphasic in timing and are similar to those reactions we have previously described for other insect bites and stings.78

Quiz Ref IDThere are few data to support bed bugs as vectors for transmission of human disease agents. After feeding on an infectious blood meal, bed bugs excrete hepatitis B surface antigen in their feces and could be a possible source of HBV infection by contamination of skin lesions or mucosal surfaces, or by inhalation of dust. However, their transmission of a human disease is yet to be firmly established.

The use of any treatment strategy for symptomatic bed bug bites has not been established. The largest series described an experience with only 17 patients. Although patients often improve after therapy with oral or topical corticosteroids and antihistamines, there are reports in which these treatments are unsuccessful.17,18 In 1 article of 2 patients with dermal reactions to bed bug bites, one was treated with prednisolone and the other was not treated.10 Reactions subsided within 2 weeks in both patients.

Bed bugs are likely to be more problematic in the future due to travel, immigration, and insecticide resistance. The most crucial need for research is in determining its vector competence.1,2,48 Development of effective repellents and public education about bed bugs are also important goals. Research is needed to elucidate the pathogenesis of clinical reactions to bed bug bites so that optimal therapy may be identified.

Author Contributions: Dr Goddard had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design, acquisition of data, analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content, and administrative, technical, or material support: Goddard, deShazo.

Financial Disclosures: None reported.

Additional Information: This article has been approved for publication as manuscript No. J-11504 by the Mississippi Agriculture and Forestry Experiment Station, Mississippi State University, Mississippi State.

Additional Contributions: Leigh Wright, BS (Department of Medicine, University of Mississippi Medical Center), offered invaluable help in the literature searches and preparation of the manuscript. Ms Wright did not receive any compensation for her contribution.

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